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Papers of the Week


Papers: 2 Nov 2024 - 8 Nov 2024


2024 Nov 04


Naunyn Schmiedebergs Arch Pharmacol


39495266

Enhancing orofacial pain relief: α-phellandrene complexed with hydroxypropyl-β-cyclodextrin mitigates orofacial nociception in rodents.

Authors

Machado BG, Passos FRS, Antoniolli ÂR, Menezes Pereira EW, Santos TKB, Monteiro BS, de Souza Siqueira Lima P, Matos SS, Duarte MC, de Souza Araújo AA, da Silva Almeida JRG, Oliveira Júnior RG, Coutinho HDM, Quintans-Júnior LJ, de Souza Siqueira Quintans J

Abstract

Orofacial pain affects 10-15% of adults and can severely impact quality of life. Despite ongoing treatment challenges, monoterpene alpha-phellandrene (PHE) shows potential therapeutic benefits. This study aimed to develop and evaluate an inclusion complex of PHE with hydroxypropyl-beta-cyclodextrin (PHE-HPβCD) for treating orofacial pain. The PHE-HPβCD complex was created using physical mixing and characterized by differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC) to determine encapsulation efficiency. The complex exhibited a 70.45% encapsulation efficiency. Male Swiss mice were used in models of orofacial pain induced by formalin, cinnamaldehyde, glutamate, and corneal nociception by hypertonic saline. Additionally, cytokine levels (TNF-α and IL-1β) were measured in the upper lip tissue of mice subjected to the formalin model. Both PHE and PHE-HPβCD showed significant antinociceptive effects at a 50 mg/kg dose during formalin-induced pain, reducing both neurogenic and inflammatory phases of pain. PHE-HPβCD also reduced TNF-α and IL-1β levels. For cinnamaldehyde and glutamate-induced nociception, both treatments reduced pain behavior, but only PHE-HPβCD decreased eye wipes in corneal nociception. These results suggest that PHE, especially in complexed form, alleviates orofacial pain by potentially modulating pain-related receptors (TRPA1 and TRPV1), mediators, like glutamate, and reducing pro-inflammatory cytokines. Further research is needed to explore the precise mechanisms of PHE in chronic orofacial pain models, but the study indicates promising avenues for new pain treatments.